This book covers the broad field of cellular, molecular, preclinical, and clinical imaging either associated with or combined with photodynamic therapy (PDT). It showcases how this approach is used clinically for cancer, infections, and diseases characterized by unwanted tissue such as atherosclerosis or blindness. Because the photosensitizers are also fluorescent, the book also addresses various imaging systems such as confocal microscopy and small animal imaging systems, and highlights how they have been used to follow and optimize treatment, and to answer important mechanistic questions. Chapters also discuss how imaging has made important contributions to clinical outcomes in skin, bladder, and brain cancers, as well as in the development of theranostic agents for detection and treatment of disease. This book provides a resource for physicians and research scientists in cell biology, microscopy, optics, molecular imaging, oncology, and drug discovery.

Cancer and neurological disease afflict millions of people in the United States and worldwide. In addition to the heavy toll they take on society, these diseases have devastating bodily consequences. Molecular imaging is a noninvasive means to understand the bodily phenomena driving these diseases and to recognize hopes for treatment. Optical fluorescence imaging is a type of molecular imaging that uses light to probe biological processes and states. Fluorescent contrast agents designed for specific molecular targets report on the status of disease and response to therapy.Myelin is an insulating sheath surrounding axons that aids in nervous signal transduction. Pathologies in myelin are associated with many neurological diseases, most prominently multiple sclerosis. A contrast agent has been evaluated for its ability to bind to myelin in the spinal cord and report on the quantity of myelin sheaths in vitro and in vivo. A novel synthesis of the agent, fluorescent characterization, and application to histological staining is also described. Many chemotherapeutic treatments of cancer damage DNA leading to cell death. To maintain genomic fidelity, cells have evolved multiple pathways to repair DNA damage. These pathways are active in cancer cells and can limit the therapeutic efficacy of DNA damaging drugs. One notable repair pathway is base excision repair, which excises chemically damaged bases. Optical imaging probes have been designed, synthesized, and characterized for their ability to bind to the first intermediate of the base excision repair pathway, the abasic (or AP) site. An assay has been developed to evaluate AP site-targeted probes. Their ability to report on physiologically relevant quantities of AP sites has been established in tissue culture. While this work focuses on AP sites in cancer, base excision repair is also relevant to neurological diseases including Alzheimer's and Parkinson's diseases.The optical imaging probes targeted to myelin and AP sites have potential preclinical application in new drug discovery. They can also be further developed to monitor response to therapy either in cell culture or animal models of disease. The probes could also be modified for combination use with additional imaging modalities for application in a clinical setting.

Cysteine proteases use a catalytic thiol to cleave amide bonds of protein substrates. This activity serves as an important regulatory mechanism for diverse cellular processes necessary for normal physiology. Dysregulated protease activity is a hallmark of numerous diseases, including atherosclerosis, arthritis, stroke, macular degeneration, neurodegenerative disorders, inflammatory diseases, and cancer. In the last decades, the field of activity-based proteomics has produced a number of tools for dissecting protease function. In the introductory chapter, I will discuss the current state of the field and describe the two main classes of probes for cysteine proteases: substrate-based and activity-based probes. I will then describe my own contribution to the field, which includes the design and characterization of several new and improved activity-based probes. We have applied these probes to optical imaging and biochemical characterization of three families of cysteine proteases: caspases, cathepsins and legumain. In particular, I have used these tools to aid in understanding the regulation of complex signaling pathways associated with cancer and inflammation. Caspases are key mediators of a programmed form of cell death called apoptosis. One of the key features of tumor cells is their ability to evade apoptosis, and therefore, a major therapeutic goal is to reactivate latent death pathways. We have developed fluorescent activity-based probes to image the induction of caspase activity in tumors in response to chemotherapy. In addition to non-invasive optical imaging, we have utilized these new probes to assess the kinetics of caspase activation in response to various death stimuli and identified a unique activation mechanism for the caspase-6 enzyme. Another emerging hallmark of cancer is infiltration of stromal-derived immune cells into the tumor, resulting in an inflammatory microenvironment. Crosstalk between tumor and immune cells can lead to enhanced proliferation, angiogenesis, and metastasis of tumor cells. The cysteine proteases legumain and cathepsins have been shown to play critical roles within the tumor microenvironment. I have developed new tools for optical imaging of their proteolytic activity in several cancer models as well as inflammation associated with pancreatitis. In the future, these new probes will have great value in further dissecting the roles of cysteine proteases in basic biology and disease. Since legumain and cathepsins are used as biomarkers for cancer, the ability to detect their proteolytic activity has much diagnostic and prognostic value in both pre-clinical and clinical settings. Furthermore, these new agents will be integral in validating these enzymes, particularly legumain, as drug targets.

Advances in Cancer Research, Volume 139, provides invaluable information on the exciting and fast-moving field of cancer research. Original reviews are presented on a variety of topics relating to the rapidly developing intersection between nanotechnology and cancer research, with unique sections in the new release focusing on Exosomes as a theranostic for lung cancer, Nanotechnology and cancer immunotherapy, Ultrasound imaging agents and delivery systems, Dendronized systems for the delivery of chemotherapeutics, Thermosensitive liposomes for image-guided drug delivery, Supramolecular Chemistry in Tumor Analysis and Drug Delivery, Gold nanoparticles for delivery of cancer therapeutics, and Single cell barcode microchip for cancer research and therapy. Provides the latest information on cancer research Offers outstanding and original reviews on a range of cancer research topics Serves as an indispensable reference for researchers and students alike

Cancer is a highly complex disease, and a common challenge of all cancer therapy approaches is the effective treatment of diseased areas while limiting the toxic effects to healthy tissues. Thus, many new approaches are being developed to improve the targeting of drugs to cancer cells. One of these approaches, photochemical internalization (PCI), aims to modify the intracellular distribution of drugs that are sequestered in endo/lysosomes, by induction of photochemical damage to endosomal membranes, using light in combination with a photosensitizer. The use of this technique is limited to areas and organs that are superficial and can be easily reached with an external light source. In this study, the use of Cerenkov luminescence (CLI), a form of light that is produced during the decay of certain radionuclides, was explored for the initiation of PCI. In vitro experiments, using the photosensitizer TPPS2a, initially examined cell killing effect after photodynamic therapy (PDT) and PCI in the presence of the antineoplastic agent bleomycin (BLM). Then, the pharmacokinetics of TPPS2a in tumor-bearing mice were studied using fluorescence imaging. Finally, trastuzumab and trastuzumab-F(ab’)2, two potential vehicles for the in vivo delivery of the Cerenkov light-producing radionuclide yttrium-90, were examined in vitro and in vivo in tumor-bearing mice. The results indicate that at fluence levels of 1.4 [mu]W/cm2, which are relevant to Cerenkov luminescence produced by yttrium-90, the PCI process can be induced and relocalization of bleomycin inside cells activated, thereby enhancing cell death. Quantification of in vivo measurements of photosensitizer biodistribution with optical imaging was only possible to a limited extent due to variations in absorption and scatter, restricting comparisons within the same tissue type. Experiments in mice showed that the selected radioligands were quite potent in delivering yttrium-90 to the tumor site, achieving maximum mean uptakes of 102.2±23.1% ID/g (trastuzumab) and 23.7±7.9% ID/g (F(ab’)2). In conclusion, we have shown that PCI activation at low light levels is possible, and that we have a suitable vehicle to deliver a significant amount of radiation to the tumor region. However, the use of an LED array to generate Cerenkov-like illumination for in vitro experiments does not necessarily accurately mimic the actual light delivery from real Cerenkov light in tissue. Therefore, further experiments are needed to apply realistic Cerenkov light levels as found in our animal experiments to in vitro PCI studies to confirm our initial hypothesis.

During the past two decades, there has been an increasing appreciation of the significant value that lifetime-based techniques can add to biomedical studies and applications of fluorescence. Bringing together perspectives of different research communities, Fluorescence Lifetime Spectroscopy and Imaging: Principles and Applications in Biomedical Dia

This book presents a systematic overview of the most relevant nanomaterials and their respective intrinsic properties that have been highly explored by the scientific community and pharmaceutical companies in several different modalities for cancer therapy and bioimaging. The chapters explore the synergistic effects provided by the different nanostructured materials and highlight the main in vitro and in vivo therapeutic achievements on cancer. This work also provides relevant discussion about the recent progresses and future challenges that nanotechnology faces on the conception of more efficient nanoformulations against primary tumors, circulating cancer cells and metastases.

Each year more than 180,000 new cases of breast cancer are diagnosed in women in the U.S. If cancer is detected when small and local, treatment options are less dangerous, intrusive, and costly-and more likely to lead to a cure. Yet those simple facts belie the complexity of developing and disseminating acceptable techniques for breast cancer diagnosis. Even the most exciting new technologies remain clouded with uncertainty. Mammography and Beyond provides a comprehensive and up-to-date perspective on the state of breast cancer screening and diagnosis and recommends steps for developing the most reliable breast cancer detection methods possible. This book reviews the dramatic expansion of breast cancer awareness and screening, examining the capabilities and limitations of current and emerging technologies for breast cancer detection and their effectiveness at actually reducing deaths. The committee discusses issues including national policy toward breast cancer detection, roles of public and private agencies, problems in determining the success of a technique, availability of detection methods to specific populations of women, women's experience during the detection process, cost-benefit analyses, and more. Examining current practices and specifying research and other needs, Mammography and Beyond will be an indispensable resource to policy makers, public health officials, medical practitioners, researchers, women's health advocates, and concerned women and their families.